Machine-Vision-Enabled Salt Dissolution Analysis

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Stukelj , J , Agopov , M , Yliruusi , J , Strachan , C J & Svanbäck , S 2020 , ' Machine-Vision-Enabled Salt Dissolution Analysis ' , Analytical Chemistry , vol. 92 , no. 14 , pp. 9730−9738 . https://doi.org/10.1021/acs.analchem.0c01068

Title: Machine-Vision-Enabled Salt Dissolution Analysis
Author: Stukelj, Jernej; Agopov, Mikael; Yliruusi, Jouko; Strachan, Clare J.; Svanbäck, Sami
Contributor organization: Division of Pharmaceutical Chemistry and Technology
Drug Research Program
Formulation and industrial pharmacy
Clare Strachan / Research Group
Date: 2020-07-21
Language: eng
Number of pages: 9
Belongs to series: Analytical Chemistry
ISSN: 0003-2700
DOI: https://doi.org/10.1021/acs.analchem.0c01068
URI: http://hdl.handle.net/10138/321457
Abstract: Salt formation is a well-established method to increase the solubility of ionizable drug candidates. However, possible conversion of salt to its original form of free acid or base - disproportionation - can have a drastic effect on the solubility and consequently the bioavailability of a drug. Therefore, during the salt selection process, the salt dissolution behavior should be well understood. Improved understanding could be achieved by a method that enables simultaneous screening of small sample amounts and detailed dissolution process analysis. Here, we use a machine-vision-based single-particle analysis (SPA) method to successfully determine the pH-solubility profile, intrinsic solubility, common-ion effect, pKa, pHmax, and Ksp values of three model compounds in a fast and low sample consumption (<1 mg) manner. Moreover, the SPA method enables, with a particle- scale resolution, in situ observation of the disproportionation process and its immediate effect on the morphology and solubility of dissolving species. In this study, a potentially higher energy thermodynamic solid-state form of diclofenac free acid and an intriguing conversion to liquid verapamil free base were observed upon disproportionation of the respective salts. As such, the SPA method offers a low sample consumption platform for fast yet elaborate characterization of the salt dissolution behavior.
Subject: 116 Chemical sciences
317 Pharmacy
PH-SOLUBILITY PROFILES
WATER-SOLUBLE DRUG
DICLOFENAC SODIUM
MICROENVIRONMENTAL PH
INTRINSIC SOLUBILITY
CARBOXYLIC-ACIDS
THERMAL-ANALYSIS
FORM
TRANSFORMATIONS
THEOPHYLLINE
PH-SOLUBILITY PROFILES
WATER-SOLUBLE DRUG
DICLOFENAC SODIUM
MICROENVIRONMENTAL PH
INTRINSIC SOLUBILITY
CARBOXYLIC-ACIDS
THERMAL-ANALYSIS
FORM
TRANSFORMATIONS
THEOPHYLLINE
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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